An oral-based combination chemotherapy regimen, consisting of lomustine (CCNU), etoposide (VP-16) cyclophosphamide and procarbazine, has been specifically developed for patients with AIDS-related non-Hodgkin's lymphoma (NHL). The overall objective response rate and median survival duration in 38 patients with advanced AIDS-NHL and poor prognostic factors enrolled on two studies of the regimen are comparable to previously reported intravenous chemotherapy regimens. Based on the results of the largest chemotherapy trial reported in 1997 by the ACTG in AIDS-related NHL, we plan to dose-modify the oral regimen in anticipation of improving the therapeutic index. A unique aspect of this proposal is to address the safety and utility of this regimen in adult men and women in East Africa, a region with a high burden of HIV infection and HIV-related malignancies. The attributes of the oral regimen in this setting are highly desirable and of paramount importance in medically underserved portions of the world. This proposal would support the first clinical trial in AIDS-related NHL in Uganda and Kenya with important laboratory correlative studies on: 1) underlying HIV infection including monitoring of CD4 lymphocyte counts and viral load; 2) underlying HHV-8 viral load in seropositive patients; and 3) procuring clinical samples and tumor specimens from all patients, and submitting them to the NCI-sponsored AIDS and Cancer Specimen Bank (ACSB) at the Ohio State University in Columbus, Ohio. The core is in place for the successful conduct of this proposal: Dr. Scot Remick, the PI of the project, is an expert in AIDS- related malignancies and Director of the CFAR International Clinical Coordination Center; our recent inclusion in the NCI- sponsored AIDS Malignancy Consortium (AMC), for which we plan to procure clinical and tumor samples for the ACSB and explore potential international collaborative activities with the AMC; the support of the CWRU Fogarty AIDS International Training and Research Program (AITRP); and fully functioning clinical and laboratory facilities in Uganda and Kenya. The goals are to establish response rates and toxicity profiles; to assess feasibility of treatment delivery and its impact on a large scale in the East African setting; to compare the course of (treated) AIDS-related lymphomas in Uganda and Kenya; to analyze the pathobiologic findings as prognostic factors for course of disease and/or treatment response and to analyze East African and US populations. The CWRU international programs and the CWRU - Columbia - New Jersey AIDS-Associated Malignancies Clinical Trials Unit (CCNJ-AAMCTU) are poised to serve as the springboard for potential future AMC international collaborative activities.